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E L Bockman

Publications and source records attributed to E L Bockman.

18 recordsLinked to original sources
PubMed1986

Adenosine regulates blood flow and glucose uptake in adipose tissue of dogs.

Intravenous norepinephrine increases glycerol release and blood flow in adipose tissue. The vasodilation may be an indirect effect of norepinephrine through the production of adenosine. Adenosine increases glucose uptake and inhibits lipolysis in vitro. To test whether adenosine regulates blood flow and/or metabolism in vivo, adenosine deaminase (ADA) was infused intra-arterially into the inguinal fat pads of anesthetized dogs. In unstimulated tissues, ADA (n = 7) significantly increased vascular resistance and significantly decreased glucose uptake compared with the effects of a control (boiled deaminase, n = 6) infusion. ADA completely blocked the norepinephrine-induced vasodilation (n = 6). No potentiation of basal or catecholamine-stimulated lipolysis was observed with ADA. The presence of ADA in the interstitial space was verified by analysis of lymph effluents. Interstitial levels of ADA were inversely correlated with the tissue contents of adenosine. These data support the hypothesis that adenosine is a regulator of blood flow in basal and stimulated adipose tissue. Adenosine also appears to regulate glucose uptake, but not lipolysis, in vivo.

Adenosine↗
PubMed1986

Verapamil and zero Ca2+ alter responses of cat muscle to halothane and caffeine.

Strips of soleus (slow twitch, oxidative) and gracilis (fast-twitch, glycolytic) muscle were obtained from 27 anesthetized cats and mounted in organ baths filled with oxygenated Krebs-Ringer solution (37 degrees C). The responses to caffeine, halothane (1%), caffeine in the presence of halothane, and electrical stimulation in the presence of halothane were examined in the two fiber types. These responses were compared with those observed in paired strips of muscle that had been treated with verapamil (10 or 28 microM), a slow calcium (Ca2+) channel blocker, with zero Ca2+, or with zero Ca2+ where magnesium (3.7 mM Ca2+) was added to replace the Ca2+. Halothane-induced contractures in the soleus were blocked by verapamil and zero Ca2+. Caffeine-induced contractures and tetanic contractions were attenuated in zero Ca2+ and by verapamil in both fiber types. Halothane overcame verapamil-induced reductions of caffeine contractures and tetanic contractions in both fiber types. In contrast, halothane did not overcome zero Ca2+-induced reductions in caffeine contractures or tetanic contractions in either fiber type. Furthermore, the addition of Mg2+ to the zero Ca2+ did not restore the responses. The findings with verapamil indicate that in cat muscle, both halothane- and caffeine-induced contractures and tetanic contractions are dependent on the influx of extracellular Ca2+. This extracellular Ca2+ may enter through the slow Ca2+ channels. However, because halothane in combination with caffeine or electrical stimulation overcame the effects of verapamil, there may be other sites involved.

Animals↗
PubMed1985

In vitro responses of cat skeletal muscle to halothane and caffeine.

Strips of soleus (100% type I) and gracilis (90% type II) muscle were obtained from anesthetized cats and mounted in organ baths filled with aerated Krebs-Ringer solution (37 degrees C). The contractile patterns in response to electrical stimulation (0.1 Hz, 25 V, 5 ms), caffeine, halothane, and caffeine in the presence of halothane were examined in the two fiber types. The ability of 25 microM dantrolene to alter the contractile patterns was also evaluated. In vitro contractile properties in response to electrical stimulation were similar to properties observed in situ, except that twitch tension in soleus muscle was significantly less in vitro than in situ. In the presence of halothane, type I soleus muscle developed a rapid contracture. The contracture was blocked by pretreatment with dantrolene and was reversed by addition of dantrolene at the peak of the response. Halothane-induced contractures were not observed at any time in type II gracilis. Type I soleus was also significantly more sensitive both to caffeine alone and to caffeine in the presence of halothane than was type II gracilis. In both fiber types, halothane increased the sensitivity of the muscles to caffeine. Dantrolene attenuated caffeine-induced contractures in both fiber types, but the attenuating effect was less in the presence of halothane. The findings of a halothane-induced contracture in the cat soleus and differential sensitivities of the two muscle fiber types to caffeine indicate that further studies in these two muscles may be useful for delineating the mechanisms inducing contracture in muscle from individuals susceptible to malignant hyperthermia.

Animals↗
PubMed1983

Changes in dog gracilis muscle adenosine during exercise and acetate infusion.

We have previously reported that tissue acetate content increases in the canine gracilis muscle during exercise at natural flow. We here report the effects of exercise and infusion of acetate on adenosine content. Muscles were vascularly isolated, perfused naturally, and stimulated to contract isometrically at 0.5, 1.0, or 2.0 Hz for 10 min (n = 6 each). Exercising and contralateral control gracilis muscles were freeze clamped in situ in Wollenberger tongs at the temperature of liquid N2. Force development was maintained during contraction. Resistance decreased as a function of contraction frequency, and adenosine content increased. Tissue adenosine content correlated inversely with resistance (r = -0.57, P less than 0.001), suggesting a role for adenosine in exercise hyperemia. During intra-arterial infusion of sodium acetate into resting muscle, tissue acetate and adenosine contents increased (417-2,193 and 0.88-3.07 nmol/g, respectively), and vascular resistance decreased (17.5-6.01 mmHg X ml-1/min/100 g). Acetate and adenosine contents correlated negatively with resistance (r = -0.83, P less than 0.001, and r = -0.60, P less than 0.05, respectively) and positively with one another (r = 0.58, P less than 0.05). Relative to an infusion of sodium chloride, oxygen consumption, venous PO2, and venous ionized calcium were unaffected. The vasodilatory effect of acetate may be due, in part, to its ability to increase tissue adenosine.

Acetates↗
PubMed1983

Blood flow and oxygen consumption in active soleus and gracilis muscles in cats.

The results of the present study indicate that, although there are quantitative differences, there are no fundamental, qualitative differences in the vascular and metabolic responses to muscle contraction between slow-twitch soleus muscle and fast-twitch gracilis muscle in cats. Vascularly isolated muscles were perfused under free-flow conditions and were stimulated to contract isometrically for 12 min. Venous outflow was measured with a drop counter. Resting blood flow (6.3 +/- 1.3 ml . min-1 . 100 g-1) and oxygen consumption (0.27 +/- 0.04 ml O2 . min-1 . 100g-1) in soleus muscle did not differ significantly from the respective values in gracilis muscle. Blood flow increased by as much as sixfold above control values in both soleus and gracilis muscles in response to muscle contraction. Oxygen consumption increased linearly as a function of muscle performance in both muscles. However, the oxygen cost per kilogram of force developed was about threefold greater in gracilis compared with soleus muscle. The lower oxygen cost of contraction, coupled with an apparent maximal oxygen consumption twice that of gracilis muscle, enabled soleus muscle to maintain a greater level of muscle performance.

Animals↗
PubMed1983

Tissue adenosine content in active soleus and gracilis muscles of cats.

Vascularly isolated cat soleus and gracilis muscles were stimulated to contract isometrically and were then frozen in situ. Adenosine, inosine, and hypoxanthine (nucleosides), and lactate were measured in neutralized, perchloric acid extracts of muscle. During contraction, nucleoside content increased in soleus muscle but changed little in gracilis muscle. However, adenosine content did not correlate with vascular conductance or oxygen consumption in either soleus or gracilis muscle. Adenosine content did correlate with lactate content in soleus but not gracilis muscle. The activity of AMP deaminase was highest in cat gracilis muscle and lowest in dog cardiac muscle. The activity of 5'-nucleotidase was lowest in cat gracilis muscle and highest in dog cardiac muscle. Cat soleus and dog gracilis muscles had intermediate activities of both enzymes. The findings of the present study do not support a role for adenosine in mediating prolonged active hyperemia in fast-twitch gracilis muscle of cats and cast doubt on such a role in slow-twitch soleus muscle of cats. Differences in the activities of AMP deaminase and 5'-nucleotidase provide a qualitative, biochemical explanation for apparent differences in net adenosine production among muscles composed of different fiber types and between skeletal and cardiac muscle.

5'-Nucleotidase↗
PubMed1982

Nonischemic myocardial hypoxia: coronary dilation without increased tissue adenosine.

Experiments were performed in 23 open-chest, anesthetized dogs to evaluate 1) the extent of coronary vasodilation during nonischemic hypoxia and 2) whether this dilation is associated with changes in cardiac concentrations of adenosine, inosine, and hypoxanthine. Three minutes of nonischemic myocardial hypoxia caused by selective perfusion of the left anterior descending coronary artery (LAD) with hypoxic blood (PO2 = 11.7 Torr) increased coronary flow 623%, an increase that was not significantly different from that at the peak hyperemic response following 3 min of ischemic hypoxia secondary to LAD occlusion (+534%). Concentrations for adenosine and inosine (nmol/g) in myocardium sampled during nonischemic hypoxia [0.8 +/- 0.2 (SE) and 0.8 +/- 0.2, respectively] were significantly less than values during control conditions (1.7 +/- 0.3 and 1.4 +/- 0.2). Hypoxanthine concentrations did not differ for nonischemic hypoxia and control conditions. During ischemic hypoxia concentrations for adenosine (31.2 +/- 4.9), inosine (91.0 +/- 13.6), and hypoxanthine (44.0 +/- 15.3) were considerably greater than values during nonischemic hypoxia and during control conditions. The results indicate that nonischemic hypoxia induced pronounced coronary vasodilation similar to that during ischemic hypoxia, with reduced rather than with increased tissue concentrations of adenosine and inosine. These findings suggest that reduced myocardial oxygen tension may cause dilation of coronary resistance vessels by a direct relaxant effect on arteriolar vascular smooth muscle.

Adenosine↗
PubMed1980

Increased muscle glucose uptake and lactate release after endotoxin administration.

Changes in glucose uptake and lactate and alanine release by skeletal muscle were studied in anesthetized dogs before and over a 4-h period after endotoxin administration and in time-matched controls. Blood flow was measured directly, and arteriovenous differences of glucose, lactate, alanine, and O2 were determined in hindlimb muscles by obtaining blood samples simultaneously from the carotid artery and profunda femoris veins. Skeletal muscle blood flow decreased by 29% after endotoxin, reflecting a similar average decrease in cardiac output. Mean arterial glucose decreased 31% and arterial lactate and alanine increased 201 and 123%, respectively, after endotoxin administration. Skeletal muscle glucose uptake increased 57% after endotoxin despite the progressively developing hypoglycemia. Postendotoxin lactate and alanine release were also elevated by 217 and 82%, respectively. Average O2 consumption by skeletal muscle did not change. The metabolic pattern observed after endotoxin administration suggests that the increased lactate and alanine release are likely to be related to the elevated glucose uptake and that skeletal muscle greatly influences the metabolic pattern observed during shock.

Alanine↗
PubMed1980

Free fatty acid utilization by skeletal muscle after endotoxin administration.

The effect of endotoxin administration on free fatty acid (FFA) utilization by skeletal muscle was investigated. Albumin bound [1-14C]palmitate was continuously infused into anesthetized dogs. Blood samples from the carotid artery and profunda femoris veins were obtained and blood flow through the thigh muscles was determined. After endotoxin, skeletal muscle blood flow decreased by 29%, reflecting the average decrease in cardiac output. Arterial FFA concentration in endotoxin-treated animals was significantly reduced relative to saline-treated animals. Whole-animal FFA turnover decreased up to 37% after endotoxin. FFA uptake was linearly correlated with arterial FFA concentration both preceding and following endotoxin and the slopes of the regression lines were identical. FFA uptake by skeletal muscle was significantly reduced during the early postendotoxin time period. Skeletal muscle FFA oxidation after endotoxin also tended to decrease. It is concluded that the changes in skeletal muscle FFA metabolism are most likely due to decreased arterial FFA levels after endotoxin rather than a direct effect of endotoxin on skeletal muscle.

Animals↗
PubMed1980

Myocardial adenosine and coronary resistance during increased cardiac performance.

The relation between myocardial adenosine content and coronary vascular resistance was studied in the open-chest dog. Cardiac performance was increased by aortic constriction or by intravenous infusion of isoproterenol. Coronary blood flow was measured by the microsphere tracer technique. In control animals, adenosine content and coronary vascular resistance were 0.22 +/- 0.03 nmol/g and 1.9 +/- 0.11 mmHg . ml-1 . min . 100 g, respectively. A range of myocardial oxygen consumptions of 5.3-24 ml O2 . min-1 . 100 g-1 was elicited. This was associated with a range of coronary blood flows of 33-166 ml . min-1 . 100 g-1. There was a significant negative correlation between coronary vascular resistance and the log of the myocardial adenosine content (r = 0.77). There was no transmural gradient in adenosine content in the control and aortic-constricted groups, but there was a significant adenosine gradient in the isoproterenol-infused group in which coronary input pressure was decreased. The hearts were not ischemic, as indicated by low myocardial lactate contents and a stable coronary sinus blood pH. These results provide support for a role of adenosine in the local control of the coronary circulation during increased cardiac performance.

Adenosine↗
PubMed1980

Resting blood flow and oxygen consumption in soleus and gracilis muscles of cats.

In contrast to previous reports, the results of the present study indicate that vascular responses of isolated soleus muscles of cats are functionally similar to those of gracilis muscles. Vascularly isolated muscles were perfused under free-flow conditions. Venous outflow was measured by a drop counter. Resting blood flows were similar in soleus (n = 16) and gracilis (n = 12) muscles, 6.6 +/- 1.2 and 3.8 +/- 0.6 ml . min-1 . 100 g-1, respectivley (P > 0.05). Resting oxygen consumption averaged 0.26 +/- 0.06 and 0.33 +/- 0.10 ml O2 . min-1 . 100 g-1 for soleus (n = 10) and gracilis muscles (n = 5), respectively (P > 0.05). In four animals, blood flow to soleus muscles measured by the microsphere technique was 2.0 +/- 0.3 ml . min-1 . 100 g-1 before and 4.6 +/- 2.1 ml . min-1 . 100 g-1 after isolation of its circulation. Before isolation, blood flow to gracilis muscle was 2.0 +/- 0.1 ml . min-1 . 100 g-1 after isolation of its circulation. Before isolation, blood flow to gracilis muscle was 2.0 +/- 0.1 ml . min-1 . 100 g-1. Both soleus and gracilis muscles exhibited active hyperemia. Autoregulation of blood flow in both muscles was weak. However, oxygen supply exceeded demand because oxygen consumption was maintained as blood flow decreased in response to reductions in perfusion pressure. There was no evidence of blood flow-limited oxygen consumption. Thus, the soleus muscles of the present study not only have low-resting blood flows and oxygen consumptions, but their responses to physiological stimuli are similar to those of gracilis muscles.

Animals↗
PubMed1976

Adenosine relaxation of isolated vascular smooth muscle.

Adenosine relaxed hog carotid media strips contracted with norepinephrine (NE) and potassium (K+). Adenosine (3 X 10(-6)M) was more effective in relaxing the NE contractures than those produced by K+. In both cases, adenosine's efficacy decreased with increasing concentrations of the stimulating agent. A high adenosine concentration (1 X 10(-3)M) was necessary to elicit relaxation of completely depolarized (124 mM K+) media strips and equimolar concentrations of aminophylline caused greater relaxation than did adenosine. Adenosine inhibited the Ca2+ dose-response curves of strips stimulated with 20 mM and 30 mM K+ and its effect was dependent on the Ca2+ concentration. Neither 1 X 10(-6)M nor 1 X 10(-4)M adenosine produced any change in the cAMP content of vascular strips. Only at high concentrations did adenosine increase the cAMP content of vascular strips, but the increase was signficantly more than that observed with the same dose of aminophylline. The present results are consistent with the possibility that adenosine relaxes vascular smooth muscle by directly altering Ca2+ permeability and/or membrane potential; they do not support a role for cAMP in the adenosine-induced relaxation of vascular smooth muscle.

Adenosine↗
PubMed1976

Adenosine and active hyperemia in dog skeletal muscle.

Adenosine as a possible mediator of active hyperemia in skeletal muscle was studied in hindlimbs of dogs. Sciatic nerve stimulation decreased vascular resistance to 55 +/- 5% (mean +/- SE) of the control value in hindlimbs perfused at a constant flow rate (61 +/- 6 ml/min). Venous plasma K+ concentrations were elevated after 2 min (from 4.0 +/- 0.2 to 4.8 +/- 0.2 meq/liter; P is less than 0.005) and 20 min (4.7 +/- 0.2 meq/liter; P is less than 0.001) of contraction, but the arteriovenous difference in plasma osmolality was changed only after 2 min of contraction (from -3.0 +/- 0.6 to -7.2 +/- 0.8 mosmol/kg H2O; P is less than 0.001). The muscle adenosine contents were not significantly elevated after 5 min of contraction, but were increased after 10 min (from 1.97 +/- 0.33 to 8.35 +/- 0.97 nmol/g; P is less than 0.05) and 25 min (from 1.64 +/- 0.22 to 7.57 +/- 2.20 nmol/g; P is less than 0.05) of contraction. Thirty minutes after contraction had ceased, the adenosine contents were significantly below control values (from 2.22 +/- 0.59 to 1.51 +/- 0.40 nmol/g; P is less than 0.005). Venous plasma adenosine concentrations did not increase during muscle contraction. No relationship was found between the increase in the plasma inorganic phosphate level and the activity of the muscles. These data indicate that the adenosine content of skeletal muscle is increased by contraction, and support the concept that adenosine may be a mediator of sustained active hyperemia.

Adenosine↗
PubMed1975

Release of adenosine and lack of release of ATP from contracting skeletal muscle.

Adenosine triphosphate (ATP) has been suggested as a mediator of active hyperemia and its levels have been reported to increase in the venous plasma from contracting skeletal muscle. However, the source of the ATP is unknown. The present study indicates that a large portion of the plasma ATP is released from the formed elements of blood when the blood is collected in the presence of EDTA. When EDTA was added to blood that was previously incubated at 37 degrees C for 5 min to destroy all free ATP, the ATP level was 0.57 plus or minus 0.12 (plus or minus S.E.) nmoles/ml. However, it was possible to detect exogenously added ATP only when blood samples were collected into EDTA; collection into saline or citrate afforded no protection against ATP degradation by the ATPases of the blood. In dog hindlimb preparations perfused at constant flow or constant pressure, the venous plasma ATP of blood collected in the presence of EDTA exhibited no consistent increase during or following tetanic contraction of the muscles. In isolated, perfused rat hindlimbs, no ATP was detectable in the venous effluents from resting or contracting muscles (ATP smaller than 0.08 nmoles/ml). However, the levels of adenosine in the venous effluents were greater in contracting than in resting hindlimbs. The data indicate that it is not possible to make valid determinations of plasma ATP levels and thus, one cannot determine the role of ATP in active hyperemia based on these data. However, the currently available data from isolated muscle preparations do not support the concept that ATP is released from contracting skeletal muscle, and therefore, it is unlikely that ATP is a mediator of the metabolically-linked local regulation of skeletal muscle blood flow. The enhanced release of adenosine from contracting rat hindlimb muscles may indicate a role for this nucleoside in the regulation of blood flow in skeletal muscle.

Adenosine↗
PubMed1975

Relationship between adenosine concentration and oxygen supply in rat brain.

Since adenosine is present in normal brain tissue and cerebrosipinal fluid and since it dilates the pial vessels, it is possible that adenosine, in addition to H-+, is also a mediator of the metabolic regulation of cerebral blood flow. Evidence supporting this hypothesis was obtained under various experimental conditions characterized by achange in brain oxygen supply. The brain was frozen in situ by means of a small bonerongeur precooled in liquid N2 and the tissue was processed for adenosine determination (nmol/g of tissue). Electrical stimulation of the cortex at 0, 15, 30, and 45 Hz yielded adenosine levels of 5.4 plus or minus 0.7, 10.5 plus or minus 1.7, 13.0 plusor minus 1.2, and 9.0 plus or minus 2.1 nmol/g. Arterial pressures of 87, 60, and 40mmHg gave adenosine levels of 7.5 plus or minus 0.76, 13 plus or minus 2.6, and 26.6plus or minus 3.3, respectively. Ventilation with 29.7, 20, 10.7, and5.5% O2 significantly increased the adenosine levels to 9.4 plus or minus 3.0, 6.4 plus or minus 1.2, 30.0 plus or minus 9.3, and 63.3 plus or minus 18.2 nmol/g, respectively. Hyperventilation significantly increased adenosine form 6.7 plus or minus 1.0 to 11.8 plus or minus 1.4 nmol/g. This increased adenosine level was reduced by additionof CO2 to the ventilating gas mixture. Lactate, the main H-+ donor, pyruvate, and cAMP changed in a fashion parallel to adenosine. However, cAMP showedonly a small increase in adenosine. These findings are in accordance with the concept that adenosine and H-+ may act synergistally to regulate cerebral blood flow and that endogenous adenosine may exert a small effect on cAMP formation.

Adenosine↗
PubMedDate not supplied

Transmural adenosine with increased cardiac work.

In hearts with five different levels of myocardial performance there was an inverse correlation between myocardial adenosine content and coronary vascular resistance. Higher levels of oxygen consumption were associated with higher myocardial adenosine content and lower coronary vascular resistance. Adenosine was uniformly distributed across the myocardial wall under all conditions, except those involving increased oxygen consumption with concomitant decreased coronary input pressure, as was observed with isoproterenol infusion. Under these conditions the adenosine content of the inner wall was significantly higher than the outer wall.

Adenosine↗